Histological and histochemical techniques recently developed by the principal investigators will be employed in experiments designed to elucidate the mechanisms responsible for failure of axonal regeneration in the adult mammalian retina following retinal injury. The retina is a part of the central nervous system (CNS) and has distinct advantages as a model system for studying CNS regeneration. Information about the retina may relate to the CNS in general. In experiments on adult mice silver-stained flat mounts of the retina will be examined to determine whether severed axons in the retinal nerve fiber layer (NFL) can be induced to regenerate into a more favorable growing environment in the vitreous chamber. Other experiments will determine if peripheral nerve axons, which normally regenerate well, can be induced to grow within the retinal NFL. These experiments will help to assess whether the optic axon has the potential to regenerate and whether the axonal environment has the potential to support nerve regeneration. In other experiments, we will apply newly developed selective histochemical techniques for demonstrating cell processes and their extracellular matrices in transmission and scanning electron microscopy. The pattern of cell processes and their substratum in the NFL will be examined in normal mice and in mice with experimentally induced NFL lesions. These patterns will be compared with the patterns in animals capable of axonal regeneration - the adult newt and the embryonic chick, to determine how the arrangement of intercellular matrix and fiber processes differ in the various species in the normal and injured states.